This New Gene Therapy Has The Potential To Prevent Seizures In Patients With Uncontrolled Epilepsy
Epilepsy is one of the most prevalent neurological diseases worldwide, affecting approximately 50 million people around the globe, according to the World Health Organization (WHO). Here in the United States, about one out of every 26 people will even develop epilepsy at some point in their lifetime.
Those with epilepsy experience a disruption of nerve cell activity in the brain– which ultimately results in seizures.
And even though about two-thirds of patients diagnosed with severe epilepsy can receive relief via traditional medications, approximately one-third of patients actually do not benefit from currently available therapies.
In some of these cases, standard drugs can even worsen seizures.
Dravet syndrome is one specific kind of treatment-resistant severe epilepsy that is caused by genetic mutations and begins during the first year of life.
The syndrome, formerly known as severe myoclonic epilepsy of infancy (SMEI), can cause up to 40 seizures per hour. It is also linked to severe developmental delays and a high infant mortality rate.
Recently, though, researchers from Macquarie University’s Dementia Research Center in Sydney, Australia, conducted a new study centered around a groundbreaking treatment that may prevent seizures by clearing protein build-ups in the brain.
The work was led by Professor Lars Ittner, who has been studying the underlying causes of neurological diseases– specifically the role of built-up tau proteins– with his team for several years.
Most recently, the team discovered that a tau protein build-up causes the hyperexcitation of neurons in Alzheimer’s patients. In other words, they identified this mechanism as a significant driver in the progression of Alzheimer’s disease (AD).
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Instead of firing when stimulated, hyperexcited neurons will continuously fire. This can cause neural network dysfunction, cognitive decline, and seizures.
So, after identifying this link to AD, Professor Ittner and his researchers then set their sights on other diseases in which hyperexcitation is at play– such as epilepsy.
Built-up hyperphosphorylated tau proteins in brain microtubules have been associated with numerous neurological diseases, including several kinds of dementia.
When the phosphorylation process functions properly, it acts as a “fine-tuner,” which allows for communication between proteins.
So, when phosphoryl is in the right quantity and at the right location, it is critical for the maintenance of signaling pathways in the brain.
Too much phosphoryl, though, can have damning and toxic effects.
After a protein molecule becomes hyperphosphorylated, too much phosphoryl will stick to the protein’s surface– ultimately changing its shape and impacting the protein’s ability to bind and communicate.
Typically, phosphoryl will act as a sort of lubricant, allowing for molecules to slip apart. According to Professor Ittner, this process is similar to when hair is washed down a shower drain.
The drain can handle a few hairs at a time. But, when there is a significant build-up, they will clump together and block the pipe.
In the human brain, though, this “pipe” is actually the human neuron. And once the pipe to a neuron is blocked off, it will die– and there is currently no treatment out there to regenerate neurons.
The team’s new study, though, found that when the phosphorylation of tau protein by kinase p38y takes place at a specific location within the genome, known as Threonine 205, excitotoxicity can actually be prevented– in other words, what causes seizures.
“Recently, we designed a new gene therapy vector, and by introducing our new therapy to the brains of mice via this vector, we have been able to show we can increase production of p38y only where it is needed,” explained Professor Ittner.
Then, after the mice were treated with the novel gene therapy, the animals who suffered from uncontrolled epilepsy showed a better chance of survival. These mice also displayed significant improvements in behavioral and brain activity.
So, now that the therapy has been tested extensively and rigorously assessed by outside independent labs, the researchers are eager to move into their next phase of work.
“Our next step is to conduct a more detailed pre-clinical evaluation in preparation for clinical trials,” Professor Ittner revealed.
“It is showing tremendous promise as a treatment for acute neurological conditions, and we hope to be able to offer it initially to patients with uncontrolled epilepsy within the next five to seven years.”
To read the study’s complete findings, which have since been published in Science Advances, visit the link here.
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